Hyperestrogenism

(Estrogen Toxicity)
Basics
OVERVIEW
• “Hyperestrogenism” refers to a condition in which excessive
estrogen is present in the body
• A syndrome characterized by high serum concentration of
estrogens (estradiol, estriol, or estrone)
• Estrogens are hormones that are produced by the female (ovary,
placenta), male (testicles), by both sexes (adrenal glands), and
by some plants; most commonly recognized as a female sex
hormone that is responsible for normal sexual behavior and
development and function of the female reproductive tract; in
the male, estrogens are responsible for Leydig cell function,
which produce testosterone
• Hyperestrogenism may occur as a result of excessive estrogen
secretion in the body or administration of estrogen-containing
medications, such as diethylstilbestrol or estriol

SIGNALMENT/DESCRIPTION OF PET
Species
• Dogs
Mean Age and Range
• Older female dogs (secondary to tumors of the ovaries; follicular ovarian cysts, in which the area containing the
egg [known as the “follicle”] in the ovary develops, but ovulation does not occur normally)
• Young female dogs (secondary to follicular ovarian cysts)
• Older male dogs (secondary to tumors of the testicles)
• If from exposure to estrogenic medications, all ages, breeds, genders; toy breed exposure to owner transdermal
hormone replacement therapy patches

SIGNS/OBSERVED CHANGES IN THE PET

• Attractive to intact male dogs (intact male dogs are capable of reproducing)
• Infertility
• Prolonged heat (specifically proestrus and estrus) in females
• Decreased libido in males
• Impulse to engage in sexual behavior (known as “nymphomania”)
• Bleeding from the vulva (the external genitalia of females) and enlargement of the vulva; excessive licking of the
vulva
• Blood in the urine (known as “hematuria”), in association with benign prostatic enlargement (known as “benign
prostatic hyperplasia” or “BPH”) or low platelet count (known as “thrombocytopenia”) that may result from
effect of estrogen on bone marrow; “platelets” and “thrombocytes” are names for the normal cell fragments that
 originate in the bone marrow and travel in the blood as it circulates through the body; platelets act to “plug”
tears in the blood vessels and to stop bleeding
• Skin—non-itchy, symmetrical hair loss (known as “endocrine alopecia”); “stud dog tail”; darkened skin (known
as “hyperpigmentation”)
• Reproductive abnormalities in females—fluid buildup of the vulva (the external genitalia of females);
enlargement of the vulva; discharge from the vulva; enlargement or development of the mammary glands
(known as “gynecomastia”)
• Reproductive abnormalities in males—tumor or mass in the testicles; difference in size of the testicles; decrease
in size of the testicles (known as “testicular atrophy”); enlarged prostate; excessive development of the male
mammary glands (known as “gynecomastia”)
• Pale gums and other moist tissues of the body (known as “mucous membranes”)
• Small, pinpoint areas of bleeding (known as “petechia”)
• Fever (due to secondary bacterial infection in association with low white-blood cell counts [known as
“neutropenia”] that may result from effect of estrogen on bone marrow)
• Depression

CAUSES AND RISK FACTORS

• Follicular ovarian cysts, in which the area containing the egg (known as the “follicle”) in the ovary develops, but
ovulation does not occur normally
• Tumors of the ovaries
• Tumors of the testicles (specifically Sertoli cell tumor, but also may occur secondary to Leydig and interstitial
cell tumors)
• Administration of estrogen-containing medications or exposure to estrogen-containing medications
• Small dogs (for example, toy-breed dogs) are at increased risk of exposure to transdermal hormone replacement
therapy being used by their owners; these patches often are applied to the forearm of the person and the small
dog is exposed as a consequence of being held frequently

Treatment
HEALTH CARE
• Discontinue administration of estrogen-containing medications, if applicable
• Avoid exposure to estrogen-containing medication (such as transdermal hormone replacement therapy), if
applicable

SURGERY
• Treatment of choice for excessive levels of estrogen (hyperestrogenism) in the intact female and male is surgical
neutering; perform a “spay” or “ovariohysterectomy” for females and perform a “neuter” or “castration” for
males
• Surgical removal of only one ovary containing a tumor for females or one testicle containing a tumor for males
may be considered in valuable breeding dogs; effects of prolonged high levels of estrogen on the uterus or
remaining testicle may decrease fertility even if the abnormal gland has been removed, making prognosis for
fertility guarded

Medications
Medications presented in this section are intended to provide general information about possible treatment. The
treatment for a particular condition may evolve as medical advances are made; therefore, the medications should
not be considered as all inclusive
• Administration of antibiotics and blood products, as needed for the individual pet
• Medications (such as synthetic erythropoietin, darbopoietin, granulocyte stimulating factor) may be considered
to stimulate production of red-blood cells and/or white-blood cells in the bone marrow; lithium reportedly has
been of benefit in cases of estrogen-induced lack of production of blood cells (known as “bone-marrow aplasia”)
• Gonadotropin-releasing hormone (hormone that causes release of luteinizing hormone from the pituitary gland;
“luteinizing hormone” is a female hormone that stimulates the ovarian follicle to develop and rupture to allow
release of the egg and to produce progesterone)—unlikely to induce ovulation in cases of follicular ovarian cysts
 Follow-Up Care
PATIENT MONITORING
• Repeat serial complete blood count (CBC) analyses—to evaluate response to therapy and progression of disease
if bone marrow cell production
• Repeat serial bone-marrow evaluations may be done—to evaluate bone-marrow response including production
of red-blood cells, white-blood cells, and platelets; signs of regeneration of blood cells may not occur for weeks
to months
• Iron supplementation may be done to support regeneration of red cells
• If using red cell stimulating drugs such as darbopoietin, red and white cell regeneration will be closely
monitored
• Clinical signs of male feminization syndrome should resolve within 2–6 weeks after surgical removal of a tumor
of the testicles

POSSIBLE COMPLICATIONS
• Decreased production of blood cells by the bone marrow (known as “bone-marrow hypoplasia”) or lack of
production of blood cells (known as “bone-marrow aplasia”)
• Death

EXPECTED COURSE AND PROGNOSIS

• Lack of resolving low blood-cell counts and continued lack of response of the bone-marrow 3 weeks after
surgical removal of ovarian or testicular tumors or removal of follicular ovarian cysts (in which the area
containing the egg [known as the “follicle”] in the ovary develops, but ovulation does not occur normally)—
associated with a grave prognosis

Key Points
• Excessive levels of estrogen in the body (hyperestrogenism) may cause several conditions, many of which are
serious or even potentially life-threatening
• Complications include decreased production of blood cells by the bone marrow (bone-marrow hypoplasia) and
lack of production of blood cells (bone-marrow aplasia)

Blackwell's Five-Minute Veterinary Consult: Canine and Feline, Sixth Edition, Larry P. Tilley and Francis W.K. Smith, Jr. © 2015 John Wiley & Sons,
Inc.